Cardiovascular News Issue 59 - October 2020 (US Edition)

October 2020 | Issue 59

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6 Conference coverage: ESC 2020 Congress

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Profile: Michael Reardon

Comment: Assessing nonobstructive coronary artery disease

POPular TAVI trial prompts call for aspirin-only antiplatelet strategy post-TAVI

page 10

IVUS linked to favourable PCI outcomes, but uptake is low

A study of US Medicare patients undergoing percutaneous coronary intervention (PCI) has found that the use of intravascular ultrasound (IVUS) resulted in a lower long-term mortality, myocardial infarction (MI), and repeat revascularisation. However, the study

by Amgad Mentias (University of Iowa Carver College of Medicine, Iowa City, USA) and colleagues, published in JACC: Cardiovascular Interventions, also found that overall use of IVUS guidance cases was low, having been used in just 5.6% of all PCI patients “with a wide variation of its use among different facilities”.

Authors of a study looking at different approaches to antiplatelet therapy after transcatheter aortic valve implantation (TAVI) say that guidelines should be rewritten to reflect their finding that aspirin alone leads to fewer bleeding and thromboembolic events in these patients, rather than using both aspirin and clopidogrel.

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his was among the findings of the POPular TAVI trial, presented during a Hot Line session at the 2020 European Society of Cardiology (ESC) Congress (29 August–1 September, virtual) by coordinating investigator Jorn Brouwer (St Antonius Hospital, Nieuwegein, The Netherlands) and published simultaneously in the New England Journal of Medicine. The trial found that the use of aspirin alone after TAVI, compared to dual use of aspirin and clopidogrel, significantly reduced bleeding events and did not increase the rate of thromboembolic events.

The POPular TAVI trial investigated the optimal antithrombotic therapy in two cohorts: patients without an indication for oral anticoagulants (cohort A) and patients on chronic

Jorn Brouwer

oral anticoagulation (cohort B). Results of cohort B had been published in early 2020 and showed that the omission of clopidogrel was associated with a reduction in bleeding events and no increase in thromboembolic events. Both were powered separately for the study outcomes.

The current study (cohort A) excluded patients who had undergone coronary artery stenting using a drugeluting stent within three months, or bare metal stent within one month, prior to TAVI. The investigatorinitiated, randomised, open-label trial, which was carried out in 17 centres across Europe, involved 665 patients without an indication for oral anticoagulation, who were randomly allocated to receive aspirin alone

Jurrien ten Berg

Continued on page 2

WITH AN AIM TO UNCOVER IF IVUS USE in real-world patients is associated with improved long-term outcomes of PCI, Mentias and colleagues studied Medicare patients who underwent PCI from January 2009 to December 2017. The main outcome of the study was long-term all-cause mortality, while secondary outcomes included hospitalisation for MI, and repeat revascularisation.

In total, the study population IVUS included 1,877,177 patients who usage in PCI cases underwent PCI during the study period, with IVUS used in 105,787 5.6% of these. The IVUS-guided PCI group had a higher prevalence of most comorbidities, Mentias and colleagues write, including heart failure (28.6% vs. 25.8%), prior coronary artery disease (22.8% vs. 21.8%), prior stroke (5.1% vs. 4.2%), chronic kidney disease (21.1% vs. 19.3%), chronic lung disease (22.9% vs. 20.9%), and pulmonary hypertension (4.8% vs.

3.9%;p<0.001 for all). The IVUS-guided PCI group also a had higher prevalence of complex PCI as Continued on page 3

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October 2020 | Issue 59

Conference coverage

POPular TAVI trial prompts call for aspirin-only antiplatelet strategy post-TAVI Continued from page 1

(331 patients) or aspirin with three months of clopidogrel (334 patients).

Primary outcomes were all bleeding and non-procedural bleeding, and secondary outcomes were a composite of cardiovascular mortality, non-procedural bleeding, stroke or myocardial infarction, and cardiovascular mortality, ischaemic stroke, or myocardial infarction.

“In cohort A of the POPular TAVI trial, we hypothesised that an aspirin alone strategy, as compared to aspirin plus three months of clopidogrel, is superior for bleeding, noninferior for the composite of cardiovascular mortality, nonprocedural bleeding, stroke or myocardial infarction, and non-inferior for the composite of cardiovascular mortality, ischaemic stroke or myocardial infarction,” Brouwer told the congress audience during a recorded presentation.

Summarising the results, Brouwer told attendees that all bleeding occurred in 15.1% of patients in the aspirin alone group, compared to 26.6% in the aspirin plus clopidogrel group, and was significantly reduced with an aspirin only strategy (risk ratio [RR]: 0.57, p-value=0.001). Additionally, non-procedural bleeding occurred in 15.1% in the aspirin alone group, versus 24.9% in the aspirin plus clopidogrel group, and was also significantly reduced with an aspirin alone strategy, Brouwer said (RR: 0.61, p-value=0.005).

The composite of cardiovascular mortality, nonprocedural bleeding, stroke or myocardial infarction occurred in 23% in the aspirin alone group versus 31.1% in the aspirin plus clopidogrel group, while the composite of cardiovascular mortality, ischaemic stroke, or myocardial infarction occurred in 9.7% in the aspirin alone group, versus 9.9% in the aspirin plus clopidogrel group.

“The conclusions of cohort A of the POPular TAVI trial, as with cohort B, were an oral anticoagulation alone strategy without clopidogrel was associated with a reduction of bleeding events and no increase in thromboembolic events,” Brouwer commented. ”In cohort A of the trial, including patients without a chronic indication for oral anticoagulation an aspirin alone strategy, as compared to aspirin plus three months of clopidogrel also reduces the rate of bleeding events, including major life-threatening or disabling bleeding and does not increase the rate of thromboembolic events.”

Providing a commentary on the results, Anna Sonia Petronio (Azienda Ospedaliera Università Pisana, Pisa, Italy) said that the study “clarifies some aspects of TAVI treatment that were empirical until now,” but said that there

are outstanding questions to be explored. “One of these is the fact that we will need to treat younger patients,” she said. “They will need more percutaneous coronary interventions (PCIs) and we already see in the follow-up that 20% of these patients will shift to anticoagulation for new atrial fibrillation.”

The study’s principal investigator Jurrien ten Berg (St Antonius Hospital, Nieuwegein, The Netherlands) later took part in a question and answer session to discuss the findings, and was asked if the omission of clopidogrel could be justified in contemporary practice, and if the findings should have a bearing on ESC guidelines. “My straight answer would be yes,” ten Berg said. “We have shown very clear results that it does lead to more bleeds. That is both in cohort B—the patients who were on an oral anticoagulant before TAVI—and in cohort A—the patients who did not have atrial fibrillation and were on aspirin.

“We did not see a hint of a reduction of thrombotic events, so to me clopidogrel does not work in this population to prevent thrombosis on a clinical scale. The study was large enough to be confident that we should not use clopidogrel and it should be, in my opinion, in the guidelines.”

On this point, Petronius and session co-chair Franz Weidinger (Hospital Rudolfstiftung, Vienna, Austria) both offered agreement, with Petronius commenting: “I perfectly agree with the investigators that they would like to have this cleared up in new guidelines.” Weidinger added: “I also think that these are extremely important results from a very well done study because the safety issue in this elderly population is very important and you could clearly show that a reduction in bleeding is possible and safe by reducing antiplatelet therapy.”

Clopidogrel does not work in this patient population to prevent thrombosis on a clinical scale. I think the study was large enough to be confident that we should not use clopidogrel and it should be, in my opinion, in the guidelines.”

News in brief

The latest stories from the world of Cardiology

n PCI ON AN UPWARD TREND: A study of percutaneous coronary intervention (PCI) procedures carried out in both the USA and Japan between 2013 and 2017 has shone a light on the increasing volume of procedures being performed in both countries.

However, the findings point to differing drivers behind the trend in each region, with Japan seeing a large upturn in elective procedures, and an increase in non-elective procedures reported within the USA.

For more on this story go to page 4. n ESC 2020 CONGRESS: The European Society of Cardiology's 2020 Congress (ESC 2020 Congress, 29 August–1 September) took place virtually this year, and featured late-breaking studies, including EMPEROR-Reduced which looked at the use of empagliflozin in patients with heart failure and a reduced ejection fraction, and BRACE CORONA, examining the effect of angiotensin-converting enzyme (ACE) inhibitors in heart patients hospitalised with COVID-19.

For more on this story go to page 7. n OPTIMAL COHERENCE TOMOGRAPHY IN THE CATHETERISATION LABORATORY : Kevin Croce discusses the use of optical coherence tomography (OCT) in the cath lab, and considers its benefits over angiography and other imaging methods. Compared to angiography alone, he argues, OCT guided percutaneous coronary intervention (PCI) results in greater stent expansion

For more on this story go to page 15.

For more coverage from the ESC 2020 Congress turn to page 6

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2021

Issue 59 | October 2020

Journal coverage

IVUS linked to favourable PCI outcomes, but uptake is low Continued from page 1

evidenced by a higher number of stents IVUS-guided PCI in the USA. “I believe placed, higher number of vessels treated, that there are several factors that are and higher number of bifurcation and implicated in the low use of IVUS, chronic total occlusion lesions, Mentias such as lack of training or expertise in and colleagues write. obtaining and interpreting the IVUS Mentias and colleagues found that images, high cost of equipment with IVUS-guided PCI use was associated low reimbursement rates from payers, with a lower one-year mortality class of recommendation for use of compared with PCI without IVUS IVUS in societal PCI guidelines, which (11.5% vs. 12.2%; p<0.001), as has not been updated since 2011, well as being associated with lack of confidence that IVUS a lower rate of one-year would improve or change 11.5% MI (4.9% vs. 5.3%) hard end points such as vs. and one-year repeat recurrent MI or death, and 12.2% revascularisation (6% vs. time constraints in setting One-year mortality rate 6.4%; p<0.001 for both). up the equipment during of IVUS-guided The study team did the procedure,” he said.

PCI vs. PCI identify an increasing It is important to note, without IVUS trend of IVUS use Mentias added, that while throughout the course of the the study showed an uptick in study, however this was described as IVUS-use—from 3% in 2009 to 7% in only a modest change, increasing from 2012—this had subsequently plateaued 3% in 2009 to 6.9% in 2017 (p<0.01). at around 6.9% by 2017.

Out of 1,934 PCI facilities, 1,073 “To reverse this trend and to (55.5%) did not use any IVUS or used encourage more operators to adopt IVUS in <1% of PCI procedures. Among IVUS in PCI, especially complex PCI, the remaining 861 facilities, there was Centers for Medicare & Medicaid large variability in IVUS use (median, Services (CMS) and insurance 5.7%; interquartile range [IQR]: 3.1% to companies should recognise the 10.7%) with 360 (33.6%), 261 (24.3%), importance of IVUS in improving and 240 (22.4%) facilities using IVUS outcomes and start a national discussion in 1% to 5% (moderate), 5% to 10% about the appropriate reimbursement (frequent), and >10% (very frequent) of model,” Mentias added. “Interventional PCI procedures, respectively. Facilities cardiology fellowship programmes with >5% IVUS use were more likely should be encouraged to make IVUS an to be a teaching hospital (29% vs. 25%; important skill that new interventional p=0.05), and with higher bed capacity trainees should learn and master in (median 302 beds vs. 279 beds; p=0.03). everyday use, this includes obtaining Speaking to Cardiovascular News, and interpretation of the images and Mentias offered his view on the potential acting on it. The professional societies barriers preventing greater uptake of should continue to enforce the role

Aspirin-free monotherapy after coronary artery stenting is feasible and safe Aspirin-free prasugrel monotherapy following successful everolimus-eluting stent implantation demonstrated feasibility and safety without any stent thrombosis in selected low-risk patients with stable coronary artery disease (CAD). This was the conclusion of the ASET pilot study published in JACC: Cardiovascular Interventions. These findings may help to underpin larger randomised controlled studies to evaluate the aspirin-free strategy compared with traditional dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI), the study’s authors suggest.

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of intravascular imaging in PCI in educational meetings and practice guidelines.”

In an editorial comment accompanying the article in JACC: Cardiovascular Interventions, Lorenz Rӓber and Yasushi Ueki (Bern University Hospital, Bern, Switzerland) note that at present, international guidelines on myocardial

Interventional cardiology fellowship programmes should be encouraged to make IVUS an important skill that new interventional trainees should learn and master in everyday use.” revascularisation allocate a Class II recommendation for IVUS-guided PCI. “The reluctance toward a Class I recommendation may be explained by a currently limited (geographical) external validity, with a majority of RCTs [randomised controlled trials] conducted in Asia and an adoption rate that remains notably low except for in Korea and Japan,” they write.

As an observational study based on an administrative database, various limitations require consideration when interpreting the findings, they note, concluding: “Collectively, the body

he study, authored by Norihiro Kogame (Department of Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands), aimed to evaluate whether prasugrel monotherapy following successful everolimus-eluting stent implantation is feasible and safe in patients with stable CAD, as recent studies have suggested that short DAPT strategies may provide an adequate balance between ischaemic and bleeding risks. However, the study’s authors note, the complete omission of aspirin immediately after PCI has not been tested so far.

As part of the multicentre, single-arm, open-label trial, patients undergoing successful everolimus-eluting stent implantation for stable CAD with SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores <23 were included.

All participants were on standard DAPT at the time of index PCI. Aspirin was discontinued on the day of the index procedure but given prior to the procedure; prasugrel was administered in the catheterisation laboratory immediately after the successful procedure, and aspirin-free prasugrel became the therapy regimen from that moment. Patients were treated solely with prasugrel for three months.

The primary ischaemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to three months.

In total, 201 patients were enrolled from February

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of evidence investigating the role of IVUS in PCI guidance has matured and data consistently suggest that imagingguided PCI should become a mainstay of complex PCI procedures. To close the gap between evidence and clinical practice, reimbursement for imaging catheters, easy-to-use semi-automated software applications, and standardised and widespread education are crucial.”

Findings of the study have prompted a flurry of debate on social media, with Gregg Stone (Icahn School of Medicine, Mount Sinai, New York, USA) among the leading figures in interventional cardiology to pick up on the findings.

Speaking to Cardiovascular News, Stone commented: “Numerous clinical trials have demonstrated that intravascular imaging substantially improves clinical outcomes after stent implantation in complex coronary lesions. Despite these studies, multiple factors have resulted in use of intravascular imaging in a smaller than appropriate proportion of cases in the USA and Europe. These factors include suboptimal training in image interpretation and how to respond to the findings, increased procedural time, and lack of reimbursement.

“Conversely, in Japan where intravascular imaging is reimbursed and is a routine part of PCI procedures, intravascular imaging is used in >90% of cases. Hopefully, if the two ongoing large-scale trials of optical coherence tomography and IVUS compared with angiography alone are positive, the guidelines will elevate intravascular imaging to Class I, and training and reimbursement will improve. This should lead to an increase in the frequency of use of intravascular imaging during PCI, with better patient outcomes.”

2018 to May 2019, all of whom underwent PCI for stable CAD. Overall, 98.5% of patients were adherent to prasugrel at three-month follow-up, Kogame and colleagues report, and the primary ischaemic and bleeding endpoints occurred in one patient (0.5%). No stent thrombosis events occurred, the study’s authors add.

The study authors conclude: “Aspirin-free prasugrel monotherapy was feasible and safe following successful DES implantation in a population of selected patients with stable CAD with low anatomic complexity. Our findings may help underpin larger randomised controlled studies to evaluate the aspirin-free strategy compared with traditional DAPT following PCI.” In an editorial comment in JACC: Cardiovascular Interventions, Usman Baber (University of Oklahoma Health Services Center, Oklahoma City, USA) writes that the study adds to the expanding evidence base evaluation short durations of DAPT after PCI. He writes: “As the field of post-PCI DAPT continues to evolve, it is clear that ASA-free strategies following a short duration of DAPT have emerged as viable alternatives to conventional antiplatelet strategies. Ongoing studies will further clarify the optimal patients and time point after PCI wherein such an approach may be initiated. Current evidence supports at least one to three months of DAPT before ASA withdrawal and although discontinuation of ASA immediately after PCI is not yet ready for clinical application, this hypothesis warrants formal evaluation in an adequately powered clinical trial.”

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October 2020 | Issue 59

Journal coverage

Trends in PCI

USA and Japan see marked increase in PCI procedures up to 2017 Analysis of data from national registries in Japan and the USA shows a large increase in the number of percutaneous coronary intervention (PCI) procedures taking place in both countries between 2013 and 2017—and offers an insight into the differing characteristics driving the increases in both nations.

THE STUDY BY TAKU INOHARA (JAPANESE Association of Cardiovascular Intervention and Therapeutics, Tokyo, Japan), published in the Journal of the American College of Cardiology (JACC), compares temporal trends in procedural volume, patient characteristics, pre-procedural testing, procedural characteristics, and quality metrics for PCI procedures in both countries over the four-year period. According to Inohara, since it was first performed in 1977, PCI has become among the most widely-performed medical procedures throughout the world, however he notes that few international comparative data on the temporal trends of PCI use are available.

The study team took data from the National Cardiovascular Data Registry (NCDR) CathPCI registry in the USA, and the Japanese Percutaneous Coronary Intervention (J-PCI) registry of patients undergoing PCI between January 2013 and December 2017. Between 2013 and 2017, a total of 2,965,457 PCIs—ranging from 550,872 to 637,650 PCIs per year—were recorded in the US CathPCI Registry, representing an increase in the volume of PCI procedures of 15.8% throughout the USA. “The increasing trend was mainly the result of the high numbers of non-elective PCIs,” Inohara and colleagues report, noting that the number of elective procedures also increased.

In Japan the study team’s data show that between 2013 and 2017, a total of 1,071,292 PCIs were performed—ranging from 181,750 to 247,274 PCIs per year—representing an increase of 36% over the course of the study. This increase, Inohara et al note, is largely the result of an increased number of elective PCIs, which grew proportionally from 58.9% in the first quarter of 2013 to 61.2% in the last quarter of 2017.

Looking at the characteristics of the patients undergoing PCI in both countries, Inohara et al note that the Japanese cohort was significantly older and had a higher proportion of men and patients with previous PCI, diabetes, and end-stage renal disease. Conversely, the study notes, Japanese patients had a lower prevalence of hypertension, dyslipidaemia, chronic lung disease, and peripheral arterial disease.

In Japan, PCIs were less frequently performed for acute coronary syndromes (39.3% in Japan vs. 81%

in the USA p<0.001), particularly non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina, than in the USA. Discussing the findings, the study team writes: “Contrary to the previous reports that involved an earlier timeframe than our study cohort and consistently showed a decline in PCI volume, the present study demonstrated the increased number of PCIs in the USA during the timeframe between 2013 and 2017.

Downward trends in the earlier timeframe may be

We are left with two choices; interventional cardiologists are increasing volumes of PCI independent of new trials, guidelines, technologies, or international reimbursement changes; or they are reading the published data and embracing percutaneous solutions for coronary artery disease by a mechanism of cultural drift.”

Heart teams and interventional cardiologists often differ over recommendations for multivessel CAD A study comparing recommendations from a heart team versus those of an interventional cardiologist for the treatment of patients with multivessel coronary artery disease (CAD) has found differing recommendations in up to one-third of cases.

ACCORDING TO THE AUTHOR of the study published in JAMA: Network Open, Michael B Tsang (Department of Medicine, McMaster University, St Catharines, Canada), this subset of cases was associated with a greater

number of divergent opinions between interventional cardiologists and within the heart team.

The study enrolled 245 consecutive patients with multivessel CAD from a high-volume tertiary care referral centre,

related to the change in the management of stable coronary artery disease after publication of the COURAGE trial, which showed the effectiveness of medical management, the wide implementation of appropriate use criteria, and the improved efficacy of preventive measures for coronary artery disease.”

Alongside this, Inohara and colleagues write, the use of fractional flow reserve as a beneficial decisionmaking tool for determining PCI indications may have contributed to the decline in elective PCIs in the USA. They add: “This trend was confirmed in our analysis between 2013 and 2015, but we also found that total numbers of PCIs in the USA began to increase thereafter, mainly because of the numbers of nonelective PCIs.” The precise reason for the uptick in nonelective PCI procedures is unknown, the study suggests, but may be reflective of an increase in acute coronary syndrome diagnosis with an ageing population and more sensitive troponin assays.

“In addition, the increased number of patients managed with a conservative approach after the introduction of appropriate use criteria may have resulted in the higher number of unplanned revascularisations. Further investigations are necessary to assess how these long-term trends would affect patients’ clinical outcomes and use of resources,” the study adds.

In an editorial comment accompanying the study in JACC, Harold Dauerman (University of Vermont Larner college of Medicine, Burlington, USA) and Michael Mack (Baylor Scott & White Health, Dallas, USA) offer a series of potential explanations for the wider adoption of PCI after 2013. Dauerman and Mack speculate that one possibility is a rise of PCI in lieu of coronary artery bypass grafting (CABG), a possible increased prevalence of coronary artery disease in both countries, and enhanced screening of at-risk patient populations due to more widespread adoption of coronary computed tomography angiogram (CTA).

“Thus, we are left with two choices,” they suggest.

“Interventional cardiologists are increasing their volumes of PCI independent of any new trials, guidelines, technologies, or international reimbursement changes; or interventional cardiologists are reading the published data and embracing percutaneous solutions for coronary artery disease by a mechanism of cultural drift.”

Dauerman and Mack conclude: “The relentless march of new percutaneous technology and advances in structural heart disease may continue to shape the culture of coronary artery disease treatment. As new trial data emerges, it will be critical for detailed international registries, like the NCDR-J PCI collaboration, to monitor the impact of these competing influences on clinical practice and patient outcomes.”

185 of whom were patients were enrolled through a screening process; a further 60 patients were retrospectively enrolled from the centre’s database. A total of 237 patients were included in the final analysis.

Treatment decisions—which comprised coronary artery bypass grafting, percutaneous coronary intervention, and medication therapy— were made by the original treating interventional cardiologists and compared with pooled-majority treatment decisions made by eight blinded heart teams using structured online case presentations.

The randomised members of the heart teams comprised experts from three domains, with each team containing one non-invasive cardiologist, one interventional cardiologist, and one

cardiothoracic surgeon.

Tsang and colleagues conclude that the heart team’s recommended treatment for patients with multivessel coronary artery disease differed from that of the original treating interventional cardiologist in up to 30% of cases. This subset of cases, they note, “was associated with a lower frequency of unanimous decisions within the heart team and less concordance between the interventional cardiologists; discordance was more frequent when percutaneous coronary intervention or medication therapy were considered.”

Tsang and colleagues add that further research is needed to evaluate whether heart team decisions are associated with improvements in outcomes and, if so, how to identify patients for whom the heart team approach would be beneficial.

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October 2020 | Issue 59

Conference coverage

ESC 2020 Congress

ISCHEMIA trial suggests invasive approach benefits high-risk patients An invasive approach involving either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) may benefit high-risk stable ischaemic heart disease patients with moderate-to-severe ischaemia and a history of heart failure or left ventricular dysfunction. This was the conclusion put forward by Renato Lopes (Duke University, Durham, USA), presenting insights from the ISCHEMIA trial at the ESC 2020 Congress (29 August–1 September, virtual).

HOWEVER, LOPES CAUTIONED THAT DUE to the number of patients in the study, the results should be interpreted as “hypothesis-generating”, adding that further follow-up is needed to assess potential longerterm benefits of the invasive approach.

The ISCHEMIA trial tested an invasive versus a conservative strategy for patients with stable ischaemic heart disease, and showed that an initial invasive strategy did not reduce the risk of the primary outcome of cardiovascular (CV) death, myocardial infarction (MI), hospitalisation for unstable angina, heart failure, or resuscitated cardiac arrest.

According to Lopes, previous studies— including the STICHES trial—have shown that patients with left Renato Lopes

ventricular ejection fraction (LVEF) lower than 35% or New York Heart Association (NYHA) class III–IV heart failure derive long-term benefit after increased risk from revascularisation with CABG, with a 16% reduction in death at 10 years. However, he said, less is known about patients with heart failure or LVEF between 35‒45%. The ISCHEMIA trial sought to explore the benefit of an invasive strategy in this subgroup of patients.

The study team compared the risk of clinical outcomes for patients with and without a history of heart failure or left ventricular dysfunction and outcomes of an invasive versus a conservative strategy across different levels of ejection fraction, analysed as a continuous variable, and using a relaxed proportional hazards assumption for treatment variable.

ISCHEMIA enrolled a total of 8,518 patients, 5,179 who had stable ischaemic heart disease, randomised to either an initial invasive treatment strategy (2,588) or to an initial conservative strategy (2,591). “Both groups had similar rates of severe ischaemia at baseline, around 65%, and, as expected, patients with heart failure had lower median EF than patients without heart failure, 44% versus 60% respectively,” Lopes explained

No discernible effect on saphenous vein graft patency from adding ticagrelor to aspirin after CABG According to findings of the POPular CABG trial, the addition of ticagrelor to aspirin after coronary artery bypass graft (CABG) surgery did not reduce the rate of saphenous vein graft (SVG) occlusion. Principal investigator of the trial was Jurriën ten Berg (St Antonius Hospital, Nieuwegein, The Netherlands) and the findings were presented during a late breaking science session at the ESC 2020 Congress (29 August–1 September, virtual) by Laura Willemsen (St Antonius Hospital, Nieuwegein, The Netherlands).

The findings were simultaneously published in Circulation.

ACCORDING TO WILLEMSEN, POPular CABG sought to test whether better platelet inhibition—through the use of ticagrelor alongside aspirin post-CABG—could provide better SVG patency. She described ticagrelor as a potent P2Y12 inhibitor that is fastacting and has almost no interindividual variability in response profile. Ticagrelor is recommended for the treatment of acute coronary syndromes and the ESC guidelines recommend its use in patients undergoing CABG for acute coronary syndrome (ACS).

POPular CABG—an investigator initiated, multicentre, randomised, double-blind, placebo controlled trial—had the hypothesis that the addition of ticagrelor to standard aspirin after CABG reduces the rate of SVG occlusions, Willemsen told the ESC Congress audience.

The study’s primary outcome was the SVG occlusion rate at one year, assessed using coronary computed tomography angiography (CCTA). The secondary endpoint was SVG failure, defined as a composite of SVG occlusions, SVG

to the audience.

Looking at the cumulative incidence of the primary outcome, Lopes said: “In patients without heart failure, we did not find any difference in the rates of the primary outcome between an invasive and a conservative strategy. However, in patients with heart failure we can appreciate that patients assigned to an invasive strategy, who had [a] lower ejection fraction, had lower rates of the primary outcome when compared with patients assigned to a conservative strategy.”

Similar assessment was also done for all-cause death, he said, finding that in patients without heart failure there was no difference between an invasive and a conservative strategy. However, in patients with heart failure and lower EF, the study team found lower rates of all-cause death in patients assigned to an invasive strategy when compared with a conservative strategy.

Conversely, in patients with heart failure and higher EF, they observed higher rates of all cause death in patients assigned to an invasive strategy when compared to a conservative strategy.

The ISCHEMIA study does have some limitations, Lopes noted, including the possible presence of unmeasured confounding, the small number of patients and events in the heart failure and left ventricular dysfunction groups. “Therefore, our results should be interpreted with caution and as hypothesis generating,” he said.

Finally, he noted, revascularisation in the invasive strategy was a mixture of CABG and PCI, “which may differ in the their acute risks and benefits as well as in their long-term protection from future events”.

In conclusion, Lopes explained: “An invasive approach may be beneficial in this sub group of highrisk patients, with moderate-to-severe ischaemia and a history of heart failure or left ventricular dysfunction.”

revascularisations, myocardial infarction procedures a cardiopulmonary bypass in myocardial territory supplied by an was used.

SVG, or sudden death. The study team The SVG occlusion rate in the also evaluated bleeding events at 30 ticagrelor group was 10.5% (51 of 484 days and one year after CABG. SVGs) versus 9.1% in the placebo group A total of 499 patients were included (43 of 470 SVGs), OR 1.29 [95% CI: in the trial, with 248 0.73‒2.30]; p=0.38. SVG randomised to the ticagrelor failure occurred in 35 (14.2%) group and 251 to the placebo patients in the ticagrelor group group. Endpoint analysis was versus 29 (11.6%) patients in available for 220 patients in the placebo group (OR 1.22, the ticagrelor group, with a [95% CI: 0.72‒2.05]). total of 484 SVGs included in In conclusion, Willemsen the primary analysis, and for told the ESC audience, “[a] 223 patients in the placebo reduction of SVG occlusion group, with 470 SVGs. Laura Willemsen rates with the addition of Baseline and procedural ticagrelor could not be characteristics were comparable between established”. both groups, Willemsen explained, with Writing in Circulation, Willemsen a mean age of the study population and colleagues note that the POPular of 68 years. Around 87% of the study CABG trial found no discernible effect population were male. Indication for from the addition of ticagrelor to aspirin CABG was acute coronary syndrome in terms of SVG patency within the in 31% of the population and in 95% of ACS subgroup, but they added that the result “does not refute the advice of the guidelines to continue ticagrelor in patients undergoing CABG for ACS, as it is possible ticagrelor has antithrombotic and pleitropic benefits that have not relation with SVG patency.” Willemsen adds that further research is needed to determine the most appropriate treatment after CABG, “not only to optimise graft patency, but also to improve clinical outcomes.”

[A] reduction of SVG occlusion rates with the addition of ticagrelor could not be established.”

Issue 59 | October 2020

Highlights from ESC 2020 Congress BRACE CORONA backs continued use of ACE inhibitors in COVID-19 patients Among the studies presented at ESC 2020 was the BRACE CORONA trial, presented in a Hot Line session, which concluded that heart patients hospitalised with COVID-19 can safely continue taking angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).

“This is the first randomised data assessing the role of continuing versus stopping ACE inhibitors and ARBs in patients with COVID-19,” said principal investigator Renato Lopes of Duke Clinical Research Institute, Durham, USA. “In patients hospitalised with COVID-19, suspending ACE inhibitors and ARBs for 30 days did not impact the number of days alive and out of hospital.”

Mavacamten improves heart function in HCM patients Mavacamten (MyoKardia) improves heart function and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), according to results of the EXPLORER-HCM trial presented in a Hot Line session at ESC Congress 2020. “The results of this pivotal trial support a role for disease-specific therapy for obstructive hypertrophic cardiomyopathy which treats the cause instead of just managing symptoms,” said principal investigator Iacopo Olivotto of Careggi University Hospital, Florence, Italy.

Conference coverage

A rapid-fire round-up of the stories, trials and research you may have missed from the virtual ESC Congress.

Quality and COVID-19 focus for new ESC president

Use of trimetazidine does not improve outcomes in PCI patients

“The ESC has played a major role in improving the standard of cardiovascular care over the decades, through its guidelines, research, education, and its advocacy efforts, and it is my job to make sure we continue on that upward trajectory,” said the incoming ESC president Stephan Achenbach, chair of cardiology at Friedrich Alexander University (Erlangen, Germany), outlining his priorities in the role.

However, looking at immediate challenges, he acknowledged that emerging from COVID-19 pandemic remains the top priority. “The COVID-19 era requires us to make decisions for an uncertain future, which is extremely difficult. Helping to steer the ESC through this, and potential future pandemics, and emerge stronger, is very important. Preparing the ESC to be ‘ready for anything’ is a major part of my remit,” he said.

Trimetazidine administered after successful percutaneous coronary intervention (PCI) does not improve outcomes in patients with chronic or acute coronary syndromes, according to research presented at the Congress.

Principal investigator Roberto Ferrari of the University of Ferrara, Ferrara, Italy said: “The trial shows that trimetazidine does not improve outcomes or symptoms after successful PCI in patients with acute and chronic coronary syndromes.”

The COVID-19 era requires us to make decisions for an uncertain future, which is extremely difficult. Helping to steer the ESC through this, and potential future pandemics, and emerge stronger, is very important.”

EMPEROR-Reduced finds reduced mortality risk in HFrEF patients using empagliflozin A further Hot Line session saw the presentation of findings of the EMPEROR-Reduced trial, evaluating the effects of empagliflozin in patients with heart failure and a reduced ejection fraction, with or without diabetes, who were already receiving all appropriate treatments for heart failure. Principal investigator Milton Packer, Baylor University Medical Centre, Dallas, USA, said: “Empagliflozin reduced the risk of serious heart failure events by 30% and decreased the risk of serious adverse renal outcomes by 50%. This trial extends the benefits of SGLT2 inhibitors to higher-risk patients and shows a meaningful benefit on renal outcomes in patients with heart failure for the first time.”

More than

116,000 211 attendees, from countries

TMVR with Tendyne results in favourable LV remodelling Transcatheter mitral valve replacement (TMVR) with the Tendyne device (Abbott) results in favourable left-sided chamber remodelling in the majority of patients one month after implantation, a study presented at the ESC 2020 Congress has concluded. Miho Fukui (Minneapolis Heart Institute Foundation, Minneapolis, USA) and colleagues analysed data from patients who had undergone TMVR with the Tendyne device between 2015 and 2018, and assessed the changes in left ventricular end-diastolic volume, ejection fraction, left ventricular mass, left atrial volume, and global longitudinal strain at baseline and one month after TMVR using computed tomographic angiography.

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October 2020 | Issue 59

Opinion

Assessing non-obstructive coronary disease in the cath lab: A tailored approach to treat anginal symptoms Javier Escaned Comment & Analysis Javier Escaned (Hospital Universitario Clínico San Carlos, Madrid, Spain) discusses the increased interest in coronary microcirculation and non-obstructive coronary artery disease.

Why is there recent interest in coronary microcirculation and non-obstructive coronary artery disease?

For the first time, there is a general awareness among cardiologists that angina may have a non-obstructive origin. There are now tools available for diagnosis and effective treatments, and there is evidence that the quality of life of these patients can be significantly improved. The evidence has been so compelling, that it has been included in the 2019 European Society of Cardiology (ESC) Clinical Practice Guidelines on Chronic Coronary Syndromes, which provides recommendations on angina caused by coronary microcirculatory dysfunction (CMD).

Why has this not previously been the case?

Due to the relevance of coronary angiography as a diagnostic tool, ischaemic heart disease largely remained a stenosis-centred condition. New imaging developments, like computed tomography (CT) angiography, focused on the diagnosis of coronary stenosis, and physiology indices like fractional flow reserve (FFR) were not an exception: they did not inform on the presence of CMD, only about the functional relevance of the stenosis. These developments were phenomenal but kept coronary stenosis as the centre of the problem. Finally, many interventionalists adopted a therapeutic nihilist attitude: “I can treat a stenosis, but I can not treat microvascular dysfunction: why should I care?” Additionally, there were not many specific diagnostic tools for CMD broadly available, but that is changing.

What is CMD? What are the clinical subsets to consider?

Microcirculatory dysfunction is a wide term that indicates that one or more roles of the coronary microcirculation are not fulfilled. From a practical perspective, the term is too vague: there are multiple pathways of dysfunction, each requiring a specific test and, subsequently, a specific

approach. In patients with chronic coronary syndromes the two main CMD endotypes are structural remodelling of the microvasculature and vasomotor disorders with an origin in endothelial or smooth muscle cell dysfunction.

How does CMD affect patients?

It is a frequent cause of anginal symptoms and an impaired quality of life that can be substantially improved if a CMD endotype is identified and followed by stratified treatment. Studies

performing a longitudinal follow-up of patients with objective evidence of CMD have demonstrated that it has major prognostic implications. At a difference of symptoms, it is still unclear if the prognostic implications of CMD can be modified by specific treatment.

Do you need invasive studies, or can you rely on non-invasive testing?

PET-based measurement of coronary blood flow is the best non-invasive approach to diagnose CMD, but, it is seldom available. Methods based on abnormal LV segment performance may not detect globally distributed CMD. Of note, as acetylcholine testing is contraindicated in non-invasive tests, vasomotor disorders cannot be explored and identification of CMD is limited to the structural endotype. The advantage of intracoronary testing is that it constitutes a one-stop-shop to explore the relevance of intermediate stenoses, explore vasomotor tone with acetylcholine, and rule out structural microcirculatory abnormalities.

What information can you obtain to diagnose CMD with PressureWire X (Abbott)?

The PressureWire X is fitted with a sensor that measures both intracoronary pressure and temperature. It can be used in patients with angiographically normal arteries or with coronary stenoses.

The diagnosis of structural CMD with the PressureWire X is based on the measurement of coronary flow reserve

It is foreseeable that in the near future patients with high IMR after successful primary PCI will be managed with specific treatments that aims to reduce this acute form of CMD.”

(CFR) and the index of microcirculatory resistance (IMR). An estimate of coronary flow, mean transit time (Tmn), is obtained using the thermodilution principle by performing saline injections from the guiding catheter while the pressure wire is inside the vessel. For CFR, measurements of Tmn are obtained at rest and during maximal hyperaemia.

For IMR, only the hyperaemic Tmn and the intracoronary pressure are used for the calculation. Abnormal values are CFR≤2.0 and IMR≥25 units. (Figure 1) Finally, the diagnosis of a vasomotor CMD endotype is based on the administration of intracoronary acetylcholine to assess the presence of endothelial dysfunction and epicardial spasm. Electrocardiogram (ECG) monitoring and repeated angiograms after each acetylcholine dose are required to assess the development of ischaemia, overt epicardial spasm, and changes in vessel diameter or TIMI flow.

What is the value of the Coroventis system (Abbott)?

The Coroventis system is a dedicated console that establishes a wireless connection with the PressureWire X. It allows you to diagnose epicardial disease and microvascular dysfunction in a single system. In addition to calculating FFR and RFR, it calculates CFR and IMR from the thermodilution and pressure data, either as outlined above and alsoor through alternative methods, like using a continued infusion of saline through a dedicated microcatheter. Currently, the Coroventis system is an indispensable element in using the PressureWire X to assess CMD. (Figure 1)

How do you integrate information obtained to clinical management of the patient?

In the structural CMD endotype, betablockers, are the first choice to control angina. In the vasomotor CMD endotype and epicardial spasm, calcium channel blockers and nitrates are used to control symptoms. In both CMD endotypes, statins, ACE inhibitors, control of cardiovascular risk factors and changes in lifestyle are recommended.

What are the next steps in this field?

Physiological assessment of the left anterior descending coronary artery in a patient with angina, abnormal exercise test and absence of coronary stenoses. Data acquisition and analysis were performed with the Pressurewire X and the Coroventis console. The figure shows three resting thermodilution curves (blue) with a Tmn of 0.57 seconds, and 3 hyperemic curves with a shorter Tmn (0.36 seconds) indicating increased flow during adenosine infusion. Coronary flow reserve (CFR) and the index of microculatory resistance were abnormal, suggesting the presence of abnormal endothelium-independent vasodilation which is characteristic of the structural CMD endotype

There is evidence that assessment of the microcirculation downstream the culprit vessels of ST-elevation myocardial infarction (STEMI) informs on the presence of the so-called microvascular obstruction phenomenon (MVO). It is foreseeable that in the near future patients with high IMR after successful primary PCI will be managed with specific treatments that aims to reduce this acute form of CMD. References 1 de Waha S, Patel M, Granger CB, et al. Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials. Eur Heart J 2017; 38(47): 3502–3510.

Disclosure Javier Escaned has been issued consultancy fees from Abbott.

October 2020 | Issue 59

10 Interview

Profile

Michael Reardon A pioneer in the field of transcatheter aortic valve implantation (TAVI), Michael Reardon (professor of cardiovascular surgery, Academic Institute Methodist DeBakey Heart & Vascular Center, Houston, USA) is known for his involvement in major studies including the CoreValve, SurTAVI and Reprise III TAVR trials. He talks to Cardiovascular News about his career to date and the future of research into TAVI.

Why did you decide to become a doctor and why, in particular, did you decide to go into cardiothoracic surgery?

I started out my college career aiming to be a mechanical engineer as I have always been fascinated with how things work. Growing up, I did not know any physicians, or even how one became a physician. In college I was exposed to people on a pre-med pathway and decided that learning how people work would be more interesting than how machines work. I attended medical school at Baylor College of Medicine in 1975, at this point Michael DeBakey and Denton Cooley were both giants in the field of cardiovascular surgery. I knew I wanted to be a surgeon, so choosing cardiovascular surgery was almost a given.

Who have been your career mentors?

I had the opportunity to train for five years with Michael DeBakey and two years with Denton Cooley. I became chief of cardiothoracic surgery at Baylor College of Medicine after DeBakey retired and worked next door to Cooley. After training with both, I also got the opportunity to work with, and get to know them both personally at a faculty level. Both influenced me greatly.

In my later career, I have watched carefully and tried to emulate Michael Mack, Marty Leon and Jeff Popma in the field of transcatheter treatment of structural heart disease and Alan Lumsden as a leader in endovascular therapy.

What has been the most important development in cardiothoracic surgery during your career?

There have been many great advances in my career— the use of the left internal mammary artery (LIMA) for coronary artery bypass (CAB), mitral valve repair, better methods of cardioplegia, percutaneous coronary intervention (PCI)—but by far the most impressive to me has been TAVI and what it offers my patients.

What has been the biggest disappointment? Something you hoped would change practice but did not?

I was convinced as a young man that we would have a functional, reliable, and easy to use total artificial heart by now. We are still waiting for this, but I am very excited with developments for potential minimally invasive support devices.

What are your current research interests?

I am deeply involved in three areas of research. This includes transcatheter therapies for structural heart disease, as well as aortic diseases—I am currently the national principal investigator for a stent graft trial for type A aortic dissection—and cardiac tumours, especially complex and malignant cardiac tumours. We have the largest experience in primary cardiac sarcoma in the world and have written extensively on this topic.

You were among the principal investigators in the landmark SURTAVI clinical trial—what do you believe have

been the major insights gained from this trial?

I am the surgical principal investigator on SURTAVI (intermediate risk), Evolut low risk, Reprise III, Acurate and Portico NG. SURTAVI and Evolut Low risk together helped move TAVI into intermediate and then low-risk groups. The insights from these two randomised trials are that TAVI is extremely safe with lower early mortality than surgery with less atrial fibrillation, bleeding and stroke. Surgery still does better with pacemakers and paravalvular leakage (PVL) but both are rapidly improving for TAVI. Both trials, when taken with the results of Partner IIA and Partner 3, are amazing advances in a very short period.

What do you believe are the factors that should be taken into consideration when deciding between TAVI and surgery, as TAVI moves into the treatment of low-risk populations?

Age and potential length of life left are the main issues which are similar to the decisions surgeons face when moving from a mechanical to a biologic aortic valve replacement. A large unknown for TAVI is the longerterm durability of the valves. So far, TAVI valves seem to be tracking surgical biologic valve durability, but the TAVI populations have been older and it is still too early for definitive answers. As we get older, we have less life span left and surgical—and I will assume TAVI— biologic valves last longer. No one knows exactly why that is the case, although I think it may be a low-grade immune reaction—as we age, our immune system weakens and attacks these valves with less vigour.

The issue for TAVI will be similar to that of surgeons looking between mechanical and tissue valves—where do you draw the age line? The low risk randomised trials have a mean age of four, and one standard deviation was six years, so this may provide guidance.

What are the key unanswered questions around TAVI that future research should prioritise?

Valve durability is a key issue and all the newer trials are using at least a 10-year follow-up. Technically, how to orient TAVI valves in an anatomic commissure-tocommissure orientation, similar to surgical biologic valves, will be important.

There is a strong emphasis on the need for a multidisciplinary heart team in structural heart interventions. Why is a cardiothoracic surgeon an important part of such a team?

The surgeon has always been a critical member of the heart team for TAVI. Initially, surgeons performed a key role in participating in randomised trials both by deciding who could be randomised to surgery and also in doing the procedure. As we move to lower risk and younger patients, it is imperative to have surgical input on who does and does not fit the randomised trial population, and to consider who might do better with surgical valve replacement, as well as serving as part of the implant team.

Valve durability is a key issue and all the newer trials are using at least a 10-year followup. Technically, how to orient TAVI valves in an anatomic commissure-tocommisure orientation will be important.

What do you feel has been the most important paper published in the past year?

Issue 59 | October 2020

Interview 11

I am very biased but I think the two low risk trials, Evolut Low Risk and Partner 3 were two of the most influential papers in some time. Additionally, MITRAFR and COAPT have invigorated our approach and thoughts on secondary mitral regurgitation.

How has the COVID-19 pandemic impacted your practice?

I think COVID-19 has impacted us all. We are just coming out of our second surge in Houston. It has impacted who we could treat and slowed both our clinical and our research efforts. The personal, clinical and economic impacts will be felt for a long time.

What are the implications of COVID-19 for the management of patients with heart disease?

COVID-19 has placed a strain on our patients, hospitals and personnel. Many TAVI patients are elderly and part of the population at risk and are hesitant to enter a hospital despite having a life-threatening disease.

Looking back over your career what has been your most memorable case?

My first cardiac autotransplant for cardiac sarcoma of the left atrium. I knew in theory this would work but to do this successfully for the first time was a great thrill. It led to a lifelong interest in this rare and difficult disease.

What advice would you give to someone looking to start a career in medicine?

Medicine is a rewarding way to spend your life. I still wake up each morning excited for what we might do this day. As I near the later part of my career, my greatest problem is that there is still too much to do and too many exciting advances. It is impossible to lose interest or stop.

Outside of medicine, what are your hobbies and interests?

My main interest is family. Like most physicians I spend a lot of time at work. When not at work, I am blessed having a wife of 45 years, two daughters and four grandchildren. I set aside a minimum of at least three weeks every year for family vacation. I have been a runner for many years and was this year excited to see my youngest daughter qualify for and get accepted to run the Boston, New York, Chicago and Berlin marathons just to see them all cancelled due to COVID-19.

Fact file Current appointments

Clinical Professor, Department of Surgery, Baylor College of Medicine Clinical Professor of Thoracic Surgery, MD Anderson Cancer Institute Professor of Cardiothoracic Surgery, Weill Cornell Surgical Director of Structural Heart Disease, The Houston Medical Hospital Senior Member, The Methodist Hospital Research Institute

Memberships

American Association for Thoracic Surgery American College of Cardiology, Fellow American Heart Association European Association for Cardiothoracic Surgery European Society of Cardiology International Society for Minimally Invasive Cardiac Surgery The Heart Valve Society of America

Education

BS, Biochemistry, University of Texas at Arlington MD, Baylor College of Medicine Surgery Residency, Baylor College of Medicine Cardiothoracic Surgery Residency, Texas Heart Institute

Issue 59 | October 2020

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Structural Heart Interventions Review looks at TAVI device selection and concludes head-to-head studies needed Transcatheter aortic valve implantation (TAVI) device selection should be guided by patient and device-specific factors, a review of optimal device choice in aortic valve stenosis has concluded. Key factors to be considered include the likelihood of paravalvular leak (PVL), conduction abnormalities, coronary reaccess, long-term durability, and valve reintervention.

T

he review, which was carried out by Bimmer E Claessen (Division of Cardiology, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, USA), was published in JAMA: Cardiology and considered the currently available data and factors influencing device choice. Trials directly comparing TAVI devices will be necessary to make adequate recommendations regarding potential advantages of one device over another, as TAVI technologies continue to evolve, the study’s authors recommend.

Claessen and colleagues note that currently three commercially available TAVI device-types are approved by the US Food and Drug Administration (FDA), a balloon-expandable valve, a self-expanding valve, and most recently a mechanically-expandable valve. Other TAVI devices are currently undergoing early feasibility studies or investigational device exemption trials. Outside of the USA a growing number of devices are approved for use or are undergoing investigation, the study notes.

Balloon-expandable devices

Looking at balloon-expandable devices, the review notes that at present, the only US FDA-approved devices are the Sapien 3 and Sapien 3 Ultra (Edwards Lifesciences).

“The lower stent frame profile of the Sapien valve means coronary reaccess after TAVR [transcatheter aortic valve replacement] is generally straightforward and uncomplicated,” Claessen and colleagues note.

“The field of self-expanding valves is more diverse,” the review goes on to state. The Evolut Pro+, part of the CoreValve family of valves (Medtronic), is the only available US FDA-approved self-expanding valve to date.

These feature a supra-annular design, which may have increased effective orifice area (EOA) and lower gradients than intra-annular TAVI devices, Cleassen and colleagues report. Several other self-expanding valves are currently undergoing clinical studies in the USA, such as the Acurate neo2 valve (Boston Scientific) and Portico valve (Abbott Structural Heart). The Acurate neo2 valve has a supra-annular design and is deployed top down, allowing for control of implant depth, Claessen and colleagues note.

Mechanically-expandable devices

Turning to mechanically-expandable valves, the review describes the Lotus Edge (Boston Scientific) as “fully repositionable and retrievable”. The device recently received US FDA approval in patients at high and extreme surgical risk, and consists of a bovine trileaflet valve in a braided nitinol frame and a polycarbonate-based skirt to reduce PVL. The review then goes on to consider the long-term clinical outcomes for the various TAVI devices, but discourages direct comparison of event rates between different device types due to differences in baseline risk profiles of the patient populations between the various studies. “Given the lack of large-scale head-to-head comparisons of various TAVR devices and the rapid development of new device iterations, there is insufficient

evidence to claim superiority of one device type over another,” the study notes, adding that “as each TAVR device has unique design characteristics, certain patientrelated and anatomy-related factors may slightly favour one or several particular designs”.

Patient-specific factors

The first factor outlined as an important consideration in TAVI device selection is valve function and unknown long-term durability. “Haemodynamic parameters to evaluate TAVR prosthesis function include mean aortic valve gradient, EOA [effective orifice area] and PVL,” the study details, adding that current literature has shown lower mean gradients and larger EOAs in supra-annular, self-expanding valves vs balloon-expandable valves, although the short-term and long-term effect of this difference remains unclear.

On annular size, the second factor listed for consideration in the review, Claessen and colleagues note that device sizing is guided by annular diameter, perimeter, or area on multislice computed tomography imaging.

Turning to aortic valve and aortic root calcification, the study notes that most TAVI decives require leaflet calcification to achieve adequate anchoring and sealing.

However, it adds, in patients with significant annular or left ventricular outflow tract calcification, significant PVL may result despite using current-generation TAVI devices. Covering the next criteria, bleeding and vascular complications, the review states that prior research has shown a clear association between smaller sheath size and a reduction in the occurrence of such complications.

Considering future directions of TAVI devices, Claessen and colleagues note that as technologies to evolve, adequate evaluation of postmarket data of TAVI devices should be performed. “Head-to-head trials directly comparing TAVR devices are necessary to make adequate recommendations regarding potential advantages of one device over another.

In conclusion, the review suggests that a “multitude of factors should be considered when selecting a TAVR device in patients with symptomatic severe AS being evaluated for therapy. Optimal device selection should be guided by patient-specific, anatomic-specific, and devicespecific factors, including likelihood of PVL, conduction abnormalities, coronary reaccess, long-term durability, and valve reintervention”.

Evolut PRO (Medtronic), Lotus Edge (Boston Scientific) and Sapien 3 (Edwards) valves are compared in the review

Preliminary results of Mitral transcatheter system finds reduction in tricuspid regurgitation

TRICUSPID VALVE REPAIR WITH THE Mistral (Mitralix) percutaneous transcatheter repair device is safe and leads to a 30-day reduction of tricuspid insufficiency and improvement of right ventricular function a first-in-human study of the device has concluded.

Findings of the study, conducted by David Planer (Department of Cardiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel) and colleagues, were published in JACC: Cardiovascular Interventions.

Mistral is a catheter-based device for tricuspid regurgitation (TR) and mitral regurgitation (MR), implanted in the right or left ventricle, consisting of a delivery system and a spiral-shaped single nitinol wire 0.475mm in diameter, which approximates the tricuspid leaflets by grasping together the chordae tendineae of the valve.

Planer and colleagues studied seven patients (four women; mean age 73.14±7.4 years) with TR and high surgical risk who underwent Mistral tricuspid repair under transesophageal echocardiography guidance.

A single device was deployed in six patients, and two devices deployed in one patient. There were no procedural or 30-day adverse events, and TR was reduced by at least one grade in all patients. Effective regurgitant orifice area was reduced from median 0.52cm2 (interquartile range [IQR]: 0.40 ‒0.60cm2) at baseline to 0.15cm2 (IQR: 0.14‒0.21 cm2) at 30 days post-procedure (p<0.01), vena contracta width was reduced from 0.95cm (IQR: 0.81‒1.16cm) to 0.62cm (IQR: 0.52‒0.67 cm) (p<0.05), and regurgitant volume decreased from 49.4ml/beat (IQR: 45.2‒57.7ml/ beat) to 19.7ml/beat (IQR: 12.4‒23.9 ml/beat) (p<0.01). Right ventricular fractional area change improved from 27% (IQR: 21.3%‒33.5%) at baseline to 38.5% (IQR: 29.0%‒47.1%) at 30-day follow-up (p<0.05). Significant improvements in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire score, and six-minute walk test were seen at 30 days.

Discussing the findings, Planer notes: “In comparison with other techniques, our very preliminary Mistral device results are encouraging in terms of safety and efficacy. The Mistral device implantation technique is rather simple, as it is not limited by leaflet coaptation gap. Yet, as in other tricuspid interventions, it is highly dependent on imaging quality of the tricuspid valve and the subvalvular apparatus, which appears more challenging than in mitral interventions.”

The findings led the study team to conclude that the Mistral device transcatheter system for tricuspid repair presents favourable safety profile and short-term efficacy.

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October 2020 | Issue 59

Transcatheter tricuspid valve replacement “low risk” for complications Transcatheter tricuspid valve replacement in the setting of transtricuspid pacemaker leads without extraction or re-replacement can be performed safely with a low risk of complications, a study published in JACC: Cardiovascular Interventions has found. The study, authored by Jason H Anderson (Mayo Clinic, Rochester, USA) and colleagues, concludes that transcatheter valve replacement for valve-in-valve or valve-in-ring implantation offers a safe alternative to surgical valve replacement in the setting of pacemaker leads.

“T

ricuspid valve surgery in the current era carries a high operative risk and a poor long-term prognosis,” Anderson and colleagues write, prompting interest in transcatheter alternatives to repeated surgical intervention.

To date, the safety and feasibility of transcatheter tricuspid valve replacement in patients with previously placed transvenous pacemaker leads, particularly right ventricular leads, has been limited to case reports and a single centre case series. Consequently, they sought to examine the incidence and types of pacemaker lead complications encountered in a large multicentre registry cohort of patients undergoing the procedure.

Data were collected through the Valvein-Valve International Database registry, comprising patients with acquired and congenital heart disease who underwent transcatheter tricuspid valve replacement following tricuspid valve repair (valvein-ring) or replacement (valve-in-valve) surgery.

The primary outcome was lead-related complications during transcatheter tricuspid valve replacement. Lead complications including lead fracture and dislodgement were assessed at the time of the procedure. Lead integrity was assessed via threshold and impedance testing immediately after transcatheter tricuspid valve replacement and during

follow-up. Procedural outcomes and postimplantation prosthetic valve function were evaluated for comparison between subgroups.

Anderson and colleagues report that overall, 335 patients underwent cardiac catherisation for intended transchatheter tricuspid valve replacement, with 329 of these having valves implanted in the tricuspid valve position within a stented surgical bioprosthetic valve (n=301 [91%]), transcatheter valve (n=2 [1%]), annuloplasty ring–supported autograft or stentless replacement valve (n=4 [1%]), or previously repaired tricuspid valve (n=22 [7%]).

Of the 335 patients in the intention-totreat cohort, 131 (39%) had a pre-existing epicardial (n=70) or transvenous (n=61) pacing system in place. Of 329 implanted patients, 128 had pacing systems (39%), which were transvenous in 58 (18%).

The study team report that patients with epicardial pacing systems were younger, had more prior cardiac surgical procedures, were more likely to have prior bioprosthetic surgical implants, and surgical valve size <29mm, and had a lower incidence of atrial fibrillation or flutter than those without epicardial pacing systems.

In total, 58 patients with transvenous pacing systems underwent transcatheter tricuspid valve replacement. Of these, 27 patients did not have trans-tricuspid valve leads; four had atrial pacing leads; 13 had

ventricular leads in the coronary sinus, and 10 had surgically excluded leads implanted between the bioprosthesis and annulus at the time of replacement.

Of the 31 patients with leads passing through the tricuspid valve, three had the RV leads extracted prior to transcatheter tricuspid valve replacement, one of whom was converted to an epicardial pacing system, while the other two had the right ventricular leads reimplanted through the tricuspid valve prosthesis afterwards. In the remaining 28 patients, the right ventricular leads were entrapped between the transcatheter tricuspid valve implant and the surgical valve (n=22) or the repaired tricuspid valve (n=6).

Detailing right ventricular lead outcomes, the study team noted that three of the 28 patients (10.7%)

Jason H Anderson

This is the largest analysis evaluating the approach and safety of transcatheter tricuspid valve replacement in the setting of prior pacemaker leads.”

Patient-specific, 3D printed aortic valve model used in preparation for TAVI procedure Researchers from the University of Minnesota, with support from Medtronic, have developed a process for multi-material 3D printing of models of the heart’s aortic valve and the surrounding structures that mimic a real aortic valve.

THESE PATIENT-SPECIFIC ORGAN MODELS, which include 3D-printed soft sensor arrays integrated into the structure, are fabricated using specialised inks and a customised 3D printing process. Such models can be used in preparation for minimally invasive procedures to improve outcomes in patients.

The research was published in Science Advances, a journal published by the American Association for the Advancement of Science (AAAS).

The researchers 3D printed the aortic root, consisting of the aortic valve and the openings for the coronary arteries. The model also included part of the left

ventricle muscle and the ascending aorta.

“Our goal with these 3D-printed models is to reduce medical risks and complications by providing patientspecific tools to help doctors understand the exact anatomical structure and mechanical properties of the specific patient’s heart,” said Michael McAlpine, a University of Minnesota mechanical engineering professor and senior researcher on the study. “Physicians can test and try the valve implants before the actual procedure. The models can also help patients better understand their own anatomy and the procedure itself.”

This organ model was specifically designed to

with intentional lead entrapment had documented lead complications.

The other 25 patients had intact right ventricular leads without known impairment of lead function through a follow-up period of 15.2 months posttranscatheter tricuspid valve replacement.

Three patients died of heart failure, unrelated to the procedure or pacemaker function, during the follow-up period, the study team reports.

In terms of procedural outcomes of patients with transvenous pacing systems that did and did not have right ventricular lead entrapment, the study team notes that these did not differ between the two groups. The median main diastolic valve gradient after transcatheter tricuspid valve replacement was 3mmHg. Two patients who underwent valve-in-ring transcatheter tricuspid valve replacement demonstrated moderate or greater paravalvular regurgitation immediately following valve implantation, neither of whom had a right ventricular lead entrapment.

Discussing the findings, Anderson et al write: “This is the largest analysis to date evaluating the approach and safety of transcatheter tricuspid valve replacement in the setting of prior pacemaker leads.

Patients with trans-tricuspid valve pacing leads undergoing transcatheter tricuspid valve replacement with lead entrapment had a low prevalence of immediate procedural complications, with lead dislodgement occurring in only one in 28 patients (4%).”

The study team concludes: “In this preliminary study, we found that transcatheter tricuspid valve replacement in the setting of a trans-tricuspid valve pacemaker lead was performed safely, with a low risk for periprocedural complications, offering a transcatheter alternative to re-do surgical tricuspid valve replacement with or without lead extraction. Although low, there is a risk for lead failure after transcatheter tricuspid valve replacement, for which ongoing evaluation of the lead threshold and impedance testing should be performed.”

help doctors prepare for a transcatheter aortic valve implantation (TAVI).

The aortic root models are made by using computed tomography (CT) scans of the patient to match the exact shape. They are then 3D printed using specialised silicone-based inks that mechanically match the feel of real heart tissue which had been obtained by the researchers from the University of Minnesota’s Visible Heart Laboratories.

Physicians can use the models to determine the size and placement of the valve device during the procedure.

Integrated sensors that are 3D printed within the model give physicians the electronic pressure feedback that can be used to guide and optimise the selection and positioning of the valve within the patient’s anatomy.

“As our 3D-printing techniques continue to improve and we discover new ways to integrate electronics to mimic organ function, the models themselves may be used as artificial replacement organs,” said McAlpine, who holds the Kuhrmeyer Family chair professorship in the University of Minnesota Department of Mechanical Engineering. “Someday maybe these ‘bionic’ organs can be as good as or better than their biological counterparts.”

Issue 59 | October 2020

Opinion 15

The benefits of optical coherence tomography in the cath lab Kevin Croce Comment & Analysis Kevin Croce, director, Chronic Total Occlusion and Complex Percutaneous Coronary Intervention Program at Brigham and Women’s Hospital, Harvard Medical School, Boston, USA, discusses the use of optical coherence tomography (OCT), and considers its benefits over other imaging methods.

How does OCT work, and what is its benefit over other imaging methods?

Optical coherence tomography (OCT) is an intravascular imaging modality that utilises near-infrared light to generate high resolution images of coronary arteries. Like intravascular ultrasound (IVUS), OCT provides information about intravascular anatomy that far exceeds the level of detail obtained from conventional contrast cineangiography.

OCT generates in vivo images of coronary arteries and deployed stents with up to 10μm of spatial resolution compared to the lower 100- to 200μm resolution of IVUS. The ultrahigh resolution of OCT enables automated measurement of lumen area, and current OCT systems co-register the OCT images with the angiogram. Co-registration and automated lumen assessment provide a high resolution 4-dimensional artery visualisation of the angiogram, the OCT lumen cross section co-registered to the angiogram, a graphical plot of the lumen area and, the longitudinal artery structure (Figure 1).

Does use of OCT lead to different outcomes compared to angiography and why?

Compared to angiography alone, OCT-guided percutaneous coronary intervention (PCI) results in greater stent expansion, less residual stenosis, and a better residual fractional flow reserve (FFR)1. Larger stents and higher FFR values would be predicted to lead to improved outcomes following PCI. Registry studies show lower mortality for OCT guided PCI compared to IVUSguided and angiogram-guided PCI2. The Illumien IV study, which is randomising patients to angiogram versus angiogram plus OCT guided PCI, is currently enrolling to evaluate the impact of OCT on adverse events in a group of patients at risk for target vessel revascularisation and stent failure3.

What data is available to demonstrate its efficacy?

In addition to the investigations noted above, in the LightLab OCT study, physicians improved their assessment of potential blockages as a result of using OCT, which better informed the choice of stent size and optimal stent deployment.

Recent data from LightLab demonstrates that OCT changes diagnosis and decision-making during PCI 88% of the time compared to an angiography-based strategy. Importantly, when calcium was present in LightLab cases, OCT prompted escalation in vessel preparation strategy to a non-compliant balloon, specialty balloon, or atherectomy 47%

utilises (1) a pre-PCI OCT run to define lesion morphology and to determine stent length and diameter and (2) a post-PCI OCT run to address medial dissections, and to optimise stent apposition and expansion. PCI operators become comfortable with the MLDMAX OCT workflow after about ten cases, and the OCT workflow is greatly facilitated by computer automated measurements of lumen size and stent expansion.

Can you provide examples where OCT has been of particular benefit?

Randomised intravascular imaging studies show reduction in major adverse cardiovascular events in both complex PCI and all-comer PCI populations5,6.

One would presume that like other intravascular imaging modalities, OCT will broadly benefit all PCI patients, but this will need to be confirmed in clinical studies. Importantly, the number needed to treat for intravascular imaging guided PCI is predicted to be very favourable for complex PCI (long stents, chronic total occlusion, bifurcation) and for cases where clinical factors such as acute coronary syndromes and/ or diabetes increase risk of target vessel revascularization. We find that the high resolution of OCT provides tremendous value when treating complex anatomy, bifurcations, and in stent restenosis.

Are there limitations of using OCT, and how could these be overcome?

The near-infrared light utilised for OCT is scattered by red blood cells

Figure 1: OCT User Interface. Pre-PCI OCT showing 1-dimensional information (Panel A). Angiogram with white square curser (black arrow) denoting location of co-registered cross-sectional OCT image (Panel B).

(Panel C) Graphical representation of the artery lumen area. White arrow points to line marker that shows location of co-registered angiogram and crosssectional OCT image. (Panel D) Longitudinal artery view

percent of the time4.

How steep is the learning curve for using OCT?

OCT image acquisition and image interpretation are easy to learn.

Recent development of a standardised “MLDMAX” OCT PCI optimisation workflow, that was applied in the LightLab programme, has made the process of learning and teaching OCT much easier. MLDMAX is an acronym for the prescriptive OCT workflow that

and therefore, OCT imaging requires transient blood clearing during image acquisition. Blood clearance is typically done with contrast injection and thus historically, OCT has required increased use of contrast. OCT imaging techniques that use saline are in development, but currently, angiographic co-registration enables OCT to be done simultaneously with angiography. The MLDMAX workflow, which was employed in the LightLab study, utilises a co-registered OCT run done at the time of angiography

to decrease contrast utilisation. In many cases, the high-resolution OCT data also negates the need for multiple orthogonal angiogram views that are employed to improve the diagnostic accuracy of low resolution angiography.

How does OCT compare to other techniques on cost?

In most healthcare facilities, OCT cost is equivalent to other intravascular imaging technologies.

Do you see OCT being in wide usage in cath labs?

Intravascular imaging clearly improves outcomes in PCI patients, and metaanalyses and large registry studies strongly suggest that intravascular imaging dramatically reduces mortality following PCI2,7,8. With the overwhelming data that intravascular imaging benefits patients, it is only a matter of time until technologies like OCT become synonymous with high quality PCI9. As studies like LightLab demonstrate how OCT streamlines workflow and improves decision making, and anticipated studies such as Illumien IV further validate the clinical impact of OCT, OCT should become a routine part of PCI procedures in the near future.

What else you would like to share about LightLab?

LightLab is continuing through multiple phases looking at decision making, efficiency, and application of OCT to complex PCI. In the next few months, we are excited to share new data on the tremendous impact of OCT on treatment of in-stent restenosis, and in the midterm, we will publish the effect of the MLD MAX OCT workflow on procedure efficiency evaluating parameters such as procedure time, number angiographic runs, and contrast utilisation.

References: 1. Meneveau N, Souteyrand G, Motreff P et al. Optical coherence tomography to optimize results of percutaneous coronary intervention in patients with non-ST-elevation acute coronary syndrome: results of the multicenter, randomized DOCTORS study.

Circulation 2016; 134: 906–917.

2. Jones DA, Rathod KS, Koganti S et al. Angiography alone versus angiography plus optical coherence tomography to guide percutaneous coronary intervention: outcomes from the pan-London PCI cohort. JACC Cardiovasc Interv 2018; 11: 1313–1321.

3. Ali Z, Landmesser U, Karimi Galougahi K et al.

Optical coherence tomography-guided coronary stent implantation compared to angiography: a multicenter randomized trial in PCI—design and rationale of ILUMIEN IV: OPTIMAL PCI. EuroIntervention 2020.

4. Bezerra HG. Analysis of changes in decision-making process during optical coherence tomography-guided percutaneous coronary interventions: Insights from the LightLab Initiative. EuroPCR 2020 presentation.

5. Hong SJ, Kim BK, Shin DH et al. Effect of intravascular ultrasound-guided vs. angiography-guided everolimuseluting stent implantation: the IVUS-XPL randomized clinical trial. JAMA 2015; 314: 2155–2163.

6. Zhang J, Gao X, Kan J et al. Intravascular ultrasound versus angiography-guided drug-eluting stent implantation: the ULTIMATE trial. J Am Coll Cardiol 2018; 72: 3126–3137.

7. Darmoch F, Alraies MC, Al-Khadra Y et al.

Intravascular ultrasound imaging-guided versus coronary angiography-guided percutaneous coronary intervention: a systematic review and meta-analysis. J Am Heart Assoc 2020; 9: e013678.

8. Choi KH, Song YB, Lee JM et al. Impact of intravascular ultrasound-guided percutaneous coronary intervention on long-term clinical outcomes in patients undergoing complex procedures. JACC Cardiovasc Interv 2019; 12: 607–620.

9. Klein LW, Anderson HV, Rao SV. Performance metrics to improve quality in contemporary percutaneous coronary intervention practice. JAMA Cardiol 2020.

Kevin Croce is director of the Chronic Total Occlusion Complex PCI Program, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.

October 2020 | Issue 59

16 Market watch

First patient enrolled in TRANSFORM-1 study of MagicTouch balloon catheter

Clinical News VitalConnect begins TELESTAR-TAVR remote monitoring study

VitalConnect has announced the commencement of the TELESTARTAVR clinical study monitoring patients undergoing transcatheter aortic valve implantation (TAVI) using the VistaSolution LIVE technology. The trial aims to measure the impact of remote patient monitoring (RPM) and telehealth on patient satisfaction, clinical outcomes, and readmission rates.

According to data from the Nationwide Readmissions Database, all-cause thirty-day readmission ranged from 14.6% to 20.9% for TAVI patients, with non-cardiac causes accounting for 61.8% and cardiac causes account for 38.2% of readmissions. A retrospective analysis of 8,073 patients, who underwent TAVI, identified arrhythmia, as one of the most prominent cardiac predictors for readmission. VistaSolution LIVE provides continuous, real-time monitoring and detection of cardiac arrhythmias.

VistaSolution LIVE can also monitor up to 11 unique patient vitals, such as heart rate, respiratory rate, body temperature, and activity, VitalConnect said in a press release. This information may aid providers to monitor early signs of deterioration, predict possible complications, and adjust treatment strategy to optimise clinical outcomes.

“The TELESTAR-TAVR study is a first-of-its-kind evaluation of the role remote patient monitoring may play in improving clinical outcomes and bringing new efficiencies to patient care,” said Brijeshwar Maini (Florida Atlantic University, Boca Raton, USA).

“We are looking forward to the results of this study and the impact that RPM may have on optimising clinical outcomes and increasing patient satisfaction following TAVR.” TELESTAR-TAVR will enrol a total of 100 patients, 50 each in the control and treatment groups, with initial study results available in six months and complete study results in 12 months.

Patients will be discharged within 24 hours of their procedure, monitored for seven days with the VitalPatch RTM biosensor and then connect with their physician via secured video call using the VistaSolution LIVE at seven, fourteen and twenty-one days. Patients will then return to the hospital for an inperson follow-up visit at 30 days.

TIDES-ACS confirms performance of Hexacath’s titanium-nitride-oxide coated stent

Results of the TIDES-ACS randomised controlled trial, confirming the safety and efficacy of the Bio-Active Stent technology (Hexacath) at 18 months follow-up versus a drug-eluting stent (DES), have been published.

Conducted in 12 international sites, the study randomised 1,491 acute coronary syndrome (ACS) patients (2:1) to receive either titanium nitride oxide bio-active coated stent (Optimax, Hexacath) versus Everolimus pharmacologically active stent (Synergy, Boston Scientific) in ACS patients.

The co-primary safety endpoint (a composite of cardiac death, re-infarction and major bleeding) occurred in 3.7% of patients receiving titanium nitride oxide-coated stents versus 7.8% of those receiving EES (HR 0.64 [95% CI 0.51 – 0.80] p=0.001) demonstrating the superiority of the titanium nitride oxide bio-active stent.

“At 18 months post percutaneous coronary intervention (PCI), the TIDES-ACS results reveal that the Optimax nitride oxide coated stent is superior in patients with acute coronary syndrome compared to one of the top drug-eluting stents (Synergy) used in current interventional cardiology,” said Pasi Karjalainen, Helsinki University Hospital, Helsinki, Finland.

The co-primary non-inferiority endpoint was the rate of major adverse cardiac events (MACE): a composite of cardiac death, nonfatal myocardial infarction (MI) and ischemia-driven target lesion revascularisation (TLR) at 12 months.

The co-primary endpoint was met at 12 months, as MACEoccurred in 6.3% with OPTIMAXTM versus 7.0% with SYNERGYTM (HR 0.93 [95% CI 0.71 – 1.22] p for non-inferiority <0.001, p for superiority=0.66).

“The TIDES-ACS results show that

Hexacath's Optimax stent technology

the Optimax nitride oxide coated stent is non-inferior (MACE) in patients with acute coronary syndrome compared to one of the best-in-class drug-eluting stents (SYNERGY) used in current interventional cardiology,” said Pim Tonino, Heart Center Catharina Hospital, Eindhoven, The Netherlands.

In patients with ACS, cobaltchromium based titanium nitride oxide coated stents were non-inferior to platinum-chromium biodegradable polymer stents for major cardiac events at 12 and 18 months and were superior for the co-primary safety endpoint, the study found.

Medtronic's Intrepid valve system

Medtronic begins early feasibility study of the Intrepid transcatheter valve system

Medtronic has announced that the US Food and Drug Administration (FDA) has granted approval for an early feasibility study (EFS) of the Intrepid transcatheter tricuspid valve replacement (TTVR) system in patients with severe, symptomatic tricuspid regurgitation.

The announcement comes on shortly after the award of a Breakthrough Device Designation for the Intrepid TTVR system. The Intrepid TTVR system is an investigational device worldwide.

“We’re beginning a new journey that we believe will open the door for the potential future treatment of patients with tricuspid valve regurgitation, who constitute a significant, patient population suffering from heart valve disease today,” said Azeem Latib, section head of interventional cardiology and medical director of structural heart interventions at Montefiore Medical Center, New York, USA and co-principal investigator in the study.

“There has been much progress regarding transcatheter replacement of diseased aortic valves, but whether we can replace the tricuspid valve without open heart surgery represents a new frontier in cardiology.”

“The clinical experience generated during this initial study phase will be critical for the future of the therapy, as many of these patients are not good candidates for traditional surgical tricuspid valve interventions due to their poor right heart functions and are higher risk due to co-morbidities,” said Vinayak Bapat, chief of cardiothoracic surgery at the Minneapolis Heart Institute (Minneapolis, USA) and coprincipal investigator in the study. “We are optimistic that these early learnings will help fuel additional clinical research and device innovation around this treatable disease.”

The Intrepid transcatheter valve is under evaluation for the treatment of symptomatic mitral valve regurgitation in the Transfemoral Mitral Early Feasibility Study.

The device is implanted using a transfemoral delivery catheter, which assists physicians in delivering and placing the valve through a catheter inserted in the femoral vein.

Concept Medical has announced the enrolment of the first patient in the TRANSFORM-1 RCT (TReAtmeNt of Small coronary vessels: Randomized controlled trial FOR MagicTouch sirolimus-coated balloon).

TRANSFORM-1 is a prospective, randomised, multicentre, European study focusing on coronary artery lesions in small vessels with a head-on comparison between sirolimus-coated MagicTouch and paclitaxel-coated SeQuent Please NEO (B Braun). In total, 114 patients are planned to be randomised 1:1 for Magic Touch or SeQuent Please NEO. MagicTouch is a CE mark approved Sirolimus-coated balloon, developed using proprietary Nanolute technology.

The primary objective of the study is to compare angiographic outcomes of the devices, for the treatment of de novo coronary artery lesions in small vessels (≤2.5 mm) with respect to net gain (mm) at six months followup. Optical coherence tomography (OCT) will be conducted at baseline.

Quantitative coronary angiography (QCA) assessment will be performed at baseline (pre- and post-procedure) and at six months follow-up. Quantitative OCT assessment will be performed at baseline. Follow-up will occur at one, six and 12 months post-percutaneous coronary intervention (PCI).

The study is chaired by Patrick Serruys (National University of Ireland, Galway, Ireland) and Bernardo Cortese (San Carlo Clinic Milano, Milan, Italy) and the principal investigator is Antonio Colombo (Centro Cuore Columbus, Milan, Italy).

The index patient was enrolled at Maria Cecilia Hospital, Cotignola, Italy and underwent a successful PCI procedure on 1 September 2020.

Commenting on the enrolment, Colombo said: “Transform-1 is launching a new standard in drugcoated balloon technology; let us enthusiastically make this study move forward.”

Cortese, chairman of the study, added: “This is great news. We struggled in the last couple of years to have one of the most modern and scientific study designs that includes OCT for lesion assessment. We look forward to enrolling all the patients at the earliest by this remarkable group of investigators.”

Serruys said: “I have to give full credit to Concept Medical and its CEO Manish Doshi for allowing key opinion leaders like Bernardo Cortese, and Antonio Colombo to perform an important mechanistic study based on OCT to diagnose truly small vessels and to attempt to demonstrate in a randomised trial the superior value of the Magic Touch SCB, a drug-coated balloon (DCB) technology that uses the powerful hydrophilic sirolimus encapsulated in lipidic microsphere with a deep vessel wall penetration and a long intra parietal residency.”

Issue 59 | October 2020

Market watch 17

Product News

Abbott's MitraClip

Abbott receives CE mark for the next-generation MitraClip

Abbott has today announced it has received CE mark approval for its fourth-generation MitraClip transcatheter mitral valve repair system.

Known as MitraClip G4, the device is now approved for use in Europe and other regions that recognise CE mark as a non-surgical option for the treatment of mitral regurgitation (MR), or a leaky heart valve. The device is already approved for use in the USA. The MitraClip G4 system provides physicians in Europe with enhancements to MitraClip’s first-of-its-kind clip-based technology, building upon the device’s delivery system. In addition to offering advanced steering during implantation, the new delivery system offers four clip sizes, including two wider clips, for doctors to have a greater variety of treatment options that can be tailored to a patients’ unique mitral valve anatomy.

The newest-generation device also offers independently controlled grippers, if needed, that allow physicians to grasp one or both mitral valve leaflets at a time during the MitraClip procedure.

MitraClip is a first-of-its-kind minimally invasive transcatheter mitral valve repair (TMVr) therapy that can be a life-saving treatment option for select patients with primary or secondary MR. The small clip-based device is delivered to the heart through a vein in the leg and clips portions of the leaflets, or flaps, of the mitral valve together to reduce the backflow of blood. Once in place, MitraClip restores the proper functioning of the mitral valve and the heart’s ability to pump oxygenated blood more efficiently.

“Despite being consistently recognised as a problem in patients around the world, MR cannot be treated through the conventional method of open-heart mitral valve surgery in more than half of the people who have this condition,” said Ralph Stephan Von Bardeleben, head of the Heart Valve Center Mainz, Universitätsmedizin Mainz, Germany, who treated the first MitraClip G4 patients in the EU. “The newest MitraClip therapy offers physicians a reliable option when surgical treatment of MR isn’t possible or appropriate, and MitraClip G4’s enhancements allow further customisation of the therapy to tailor treatment to individual patient needs.”

MitraClip is backed by more than 16 years of clinical experience with proven

safety, survival and durable clinical outcomes. Data presented at PCR e-Course 2020 (25–27 June, virtual) from a real-world clinical study of over 1,000 MitraClip patients showed a high implant success rate (99%) and demonstrated MR reduction to the level of none or trace in patients with either primary MR (to ≤1+ in 87.1%) or secondary MR (to ≤1+ in 90.1%) at 30 days.

The MitraClip system has been commercially available in the USA since 2013 and in Europe since 2008.

Recent regulatory milestones for the device include the first-ever commercial introduction of MitraClip therapy to China and approval in Japan for the fourth generation of MitraClip, both in June of 2020.

Boston Scientific launches Acurate neo2 aortic valve system in Europe

Boston Scientific has announced a controlled launch of the Acurate neo2 aortic valve system in Europe. This next-generation transcatheter aortic valve implantation (TAVI) technology is a new platform designed with a number of features to improve upon the clinical performance of the original Acurate neo platform.

Compared to the previous generation device, the Acurate neo2 valve system has an expanded indication for patients with aortic stenosis—with no specified age or risk level—who are considered appropriate candidates for the therapy by their heart team, including a cardiac surgeon.

Indicated to restore function and normal blood flow through a severely narrowed aortic valve, the Acurate neo2 valve system features a new annular sealing technology designed to conform to irregular, calcified anatomies and further minimise paravalvular regurgitation or leaking (PVL). In addition, the delivery system simplifies access to smaller and complex vessels at the entry site and allows for highly accurate valve positioning while the topdown deployment mechanism further supports stable placement and release to ensure the best patient outcomes.

“We believe having this differentiated valve with the enhanced sealing technology will further drive favourable market experience and growth,” said Joe Fitzgerald, president, Interventional Cardiology, Boston Scientific.

“Combined with the Lotus Edge aortic valve system and Sentinel cerebral protection system to protect the brain against the risk of TAVI-related stroke, the Acurate neo2 valve represents the natural evolution of our complementary dual-valve TAVI toolkit that covers the needs of a wide range of patient cases.”

Data from the Acurate neo2 CE-mark study demonstrated PVL rates for the Acurate neo2 valve system to be lower

than previously reported with the current generation Acurate neo valve. At 30 days and one-year after implantation, respectively, 97% and 97.5% of patients experienced ≤ no/trace or mild PVL, 3.0% and 2.5% of patients experienced moderate PVL and 0% of patients experienced severe PVL. “We are pleased to bring the latest iteration of Acurate technology to market, offering design improvements that further support procedural performance and optimal outcomes for patients with severe symptomatic aortic stenosis, from those with simple to the most challenging anatomies,” said Ian Meredith, executive vice president and global chief medical officer, Boston Scientific. “The straightforward implant procedure also enables physicians to reduce the length of time patients need to stay in the hospital, without compromising on safety and clinical results.”

The Acurate neo2 aortic valve system received CE mark in April 2020. In the USA the Acurate neo2 valve system is an investigational device being assessed in the Acurate investigational device exemption (IDE) clinical trial and is not available for sale.

Study, which showed bicuspid patients implanted with Evolut TAVR had low rates of all-cause mortality or disabling stroke at 30 days (1.3%), a low rate of serious procedural complications, no annular ruptures or aortic dissections and no moderate/severe paravalvular leak. The study also maintained the Evolut TAVI platform’s industry-leading hemodynamics (blood flow) with patients experiencing low mean AV gradients (7.6 ± 3.7 mm Hg), and large effective orifice area (2.3 ± 0.7 cm2).

The pacemaker rate was 15.1%.

“The increased adoption of the Evolut platform globally is partially attributed to the fact that it meets the needs of a broad variety of patients including those who have unique anatomical variations,” said Jeffrey Popma, chief medical officer and vice president, medical affairs for the Structural Heart business, which is part of the Cardiac and Vascular Group at Medtronic.

US FDA approves revised labelling for Medtronic’s Evolut valve

Carillon (Cardiac Dimensions) system

Medtronic has announced that the US Food and Drug Administration (FDA) has approved revised commercial labelling for the Evolut transcatheter aortic valve implantation (TAVI) platform that modified a precaution for the treatment of bicuspid severe aortic stenosis (AS) patients at a low risk of mortality during surgical aortic valve replacement.

The revised commercial labelling includes recommendations heart teams should consider when assessing TAVI as a potential treatment option for bicuspid patients, including patients’ anatomical characteristics, age, long-term durability, and the existing clinical data.

Bicuspid aortic valve disease is a congenital heart defect that is prevalent in 1‒2 % of the population and accounts for nearly half of all severe symptomatic aortic stenosis patients in the USA. The condition is an abnormality of the aortic valve resulting in the patient having two functional valve leaflets instead of the more common three leaflets (tricuspid).

“Clinical outcomes generated to date through the TVT Registry and the Low Risk Bicuspid Trial have shown that the Evolut TAVI system achieves favourable early results for patients with bicuspid aortic valve disease,” said John Forrest, associate professor of medicine at The Yale University School of Medicine, New Haven, USA. “The updated labelling is indicative of the progress that has been made to find minimally invasive treatment options for this particular group of patients with severe AS and should be part of the decision process made by heart teams evaluating patients with bicuspid aortic stenosis.”

The revised labelling is supported by recent data from the Low Risk Bicuspid

Cardiac Dimensions receives Australian regulatory approval for its Carillon mitral contour system

Cardiac Dimensions has announced that Australia’s Therapeutic Goods Administration (TGA) has approved its Carillon mitral contour system, a right heart transcatheter mitral valve repair (TMVr) device. The device is designed to treat the primary cause of functional mitral regurgitation (FMR) in patients with mitral regurgitation grades 2+, 3+ and 4+.

“We would like to thank the Therapeutic Goods Administration for their partnership in the review and approval of the Carillon System in Australia,” said Rick Wypych, chief executive officer and president of Cardiac Dimensions. “This is a significant milestone as Australian patients with heart failure can now be treated earlier in their disease state with a minimally invasive treatment for mitral regurgitation.”

“The availability of the Carillon system is an extremely exciting advancement for the medical community as this technology has the potential to help millions of patients suffering from heart failure and FMR,” commented David Kaye, director of cardiology at The Alfred Hospital, Melbourne, Australia. “The Carillon system provides a new, non-surgical method to correct a fundamental problem with the mitral valve in patients with heart failure. This approach has been shown to reduce mitral regurgitation and to favourably impact the left ventricle (LV). This is significant because a reduction in LV enlargement in heart failure is known to be associated with positive patient outcomes.”

October 2020 | Issue 59

18 Market watch and set new industry standards for delivering an outstanding experience for clinicians, helping them to deliver superior care to every patient,” said Ronald Tabaksblat, general manager image guided therapy systems at Philips.

“The integrated platform enables us to efficiently carry out complex interventions at any time using a wide range of functions such as IVUS and iFR co-registration,” said Alexander Becker, head of the cardiac catheter laboratory at the Robert Bosch Hospital, Stuttgart, Germany, and one of the first hospitals to experience the new platform. “The use of the control panel by the examiner is intuitive, combining different sources of information to make patient evaluation much easier and faster.”

Philips adds that the new Azurion platform allows clinicians to easily switch between imaging, physiology, haemodynamic and informatics applications, including SmartCT and IntraSight—a suite of clinically proven iFR, FFR, IVUS and co-registration modalities.

Product News

Azurion (Philips) smart CT tableside monitor

The Carillon system is placed using a catheter-based technique in a vein on the outside of the heart that is adjacent to the mitral valve. This procedure is designed to reshape the mitral valve, reduce valve leakage, and thus reduce mitral regurgitation and induce favourable remodelling.

The approval was based on the combined efficacy and safety results from several Cardiac Dimensions’ studies including the most recent REDUCE FMR study. Treatment with the Carillon mitral contour system in these studies consistently demonstrated a significant decrease in regurgitant volume and left ventricular volumes, the company said in a press release. These changes were associated with reduced heart failure symptoms and improved quality of life.

Philips launches the latest version of its Azurion imaging platform

Royal Philips has announced the nextgeneration of its Azurion image-guided therapy platform, which has been designed to improve the quality and efficiency of interventional procedures.

Earlier generations of Azurion have been

used in over two million procedures worldwide, according to the company.

The Azurion image-guided therapy platform now integrates control of imaging, physiology, haemodynamic and informatics applications, as well as intuitive control of the gantry, at the tableside, allowing clinicians to control all compatible applications from a single touch screen while performing procedures. This can eliminate the need for clinicians to leave the sterile field and step into an adjacent control room, as well as supporting faster and better informed decision making, the company said in a press release.

Philips is also introducing a new 3D imaging solution called SmartCT, where users are guided through image acquisition and can review and interact with the acquired computed tomography (CT)-like 3D images on the tableside touch screen module using 3D visualisation and measurement tools. These tools have been designed to support procedures in a range of clinical domains, including neurology, oncology, and cardiovascular procedures.

“Our aim as an innovation company and global market leader in imageguided therapy is to push the boundaries

InnovHeart announces the first-in-human use of its Saturn mitral valve system

InnovHeart has announced the successful first-in-human implantation of its proprietary Saturn transcatheter mitral valve along with positive results at 30-day follow-up for the patient, a 72-year-old male suffering from severe functional mitral regurgitation.

The trans-apical transcatheter mitral valve replacement (TMVR) procedure was performed as part of an ongoing European clinical trial on 19 August 2020 at Santaros Klinikos University Hospital (Vilnius, Lithuania) with the heart team of Kęstutis Ručinskas, Audrius Aidietis, Vilius Janušauskas, and Valdas Bilkis, supported

by Paolo Denti, and Stefano Stella.

“We are grateful to have had the opportunity to work with Denti, Stella, and the InnovHeart team in order to provide a novel treatment option for this high-risk patient,” said Kęstutis Ručinskas, primary investigator and head of Cardiac Surgery

at Santaros Klinikos. “Although it was the first clinical use of the Saturn valve, the procedure was straight-forward, and the valve was implanted successfully with excellent function.”

“The Saturn implant is unique in the way it combines a transcatheter bioprosthetic valve with an annular structure to remodel the native annulus and seal the perimeter of the implant, thus eliminating mitral regurgitation and restoring optimal valve function,” said Audrius Aidietis, head of Interventional Cardiology at Santaros Klinikos. “After 30 days, the patient has already experienced a noticeable reduction in symptoms, with improvements in six-minute walk test, Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life survey and a reduction from New York Heart Association (NYHA) III to NYHA II. In addition, the valve continues to exhibit outstanding haemodynamic performance with no MR and no outflow tract obstruction.”

“Having worked with Giovanni Righini and the InnovHeart team throughout the pre-clinical development, I am pleased to have reached this important milestone together in the interest of the many patients suffering from severe mitral regurgitation,” said Paolo Denti, InnovHeart consultant and cardiac surgeon at San Raffaele University Hospital in Milan, Italy. “This was a multidisciplinary success. Every step of the procedure was methodical and controlled with standard echo and fluoro imaging. More importantly, the patient was stable throughout the procedure, despite severe ventricular dysfunction. It did not feel like a first human implant, and the short duration of the procedure speaks for itself. I am confident that the Saturn TMVR system will become a valuable new therapy with fewer exclusion criteria than other technologies, with the potential to treat a wider range of patients.”

“The initial clinical experience has been very encouraging and confirms the unique benefits the Saturn TMVR system can offer in terms of annular support, left ventricular outflow tract (LVOT) preservation, sealing capability and procedural predictability.

We look forward to providing similar comprehensive treatment for many other patients with mitral regurgitation in the future. Continued enrolment in our European Trans-Apical Pilot Study will provide valuable follow-up data and support for the ongoing development of our trans-septal delivery system, which utilises the same Saturn implant,” added Brent Ratz, InnovHeart chief executive officer.

Calendar of events Please be advised that the events listed opposite, because of COVID-19, are subject to change. Please check the relevant website for further details as the event may be cancelled, postponed, or become a virtual event.

8–10 October 34th EACTS Virtual

22–24 November PCR London Valves Virtual

11–13 February JIM Milan, Italy

28 April–1 May SCAI 2021 Scientific Sessions Chicago, USA

www.eacts.org/annual-meeting/

www.pcronline.com/Courses/PCR-

www.jim-vascular.com/

scai.org/scai-2021-scientific-

14–18 October TCT Connect Virtual www.crf.org/tct

London-Valves

2021 30 January–2 February STS annual meeting Austin, USA https://sts2021.com/

27 February–2 March CRT 2021 National Harbor, USA www.crtmeeting.org/

sessions

15–17 May ACC 2021 Scientific Sessions Atlanta, USA acc.scientificsession.acc.org

Issue 59 | September 2020

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